Osteogenesis Imperfecta

Brittle Bone Disease

By: Cheyenne Marnoch and Tayler Moyer

What is it?

A condition in which the bones are not formed fully and are not as strong as a typical person. There are eight types or forms of osteogenesis imperfecta. Type I is the most mild form, while Type II can be the most severe.
Big image


What happens to the individual due to the genetic issue? (Symptoms)

Depending on the type or form of osteogenesis imperfecta, the symptoms vary. Symptoms may vary from bone fractures as a kid to life-threatening problems with breathing.

Type I- Most Mildest Form:

  • Bones break easily
  • Collagen produced insufficently
  • Discoloration of whites of eyes
  • Poor muscle tone
  • Loose or bendy joints
  • Hearing loss, mostly in children
  • Fragile Teeth

Type II- Most Serious Type:

  • Death within first year
  • Fragile ribcage= breathing failure
  • Skull Bones = cerebral hemorrhage
  • Severe Bone deformity

Type III- More Progressive Form:

  • Born with fractures (Infants)
  • Bones Fracture easily
  • Bone deformity
  • Short Stature
  • Curve of the spine
  • Respiratory problems
  • Poor muscle tone
  • discoloration of whites of the eyes
  • Fragile Teeth
  • Loss of Hearing

Symptpms Continued

Type IV- Moderately Severe:

  • Bones fracture easily
  • Short stature
  • Curve of spine
  • Hearing loss

Type V:

  • Same features as Type IV
  • On X-Ray Bones have mesh-like appearance
  • Bones break down

Type VI:

  • Same features as Type IV
  • Bone on X-Ray appear like fish scales

Type VII:

  • Rare recessive form

Type VIII:

  • Same symptoms as Type IV

Are there any treatments?

Currently there is no cure for Osteogenesis Imperfecta, but treatments vary with the type or form involved. Treatments are generally based upon preventing fractures, controlling the symptoms, and developing more bone mass. Bisphosphonate drugs or surgery to put in place metal rods are also commonly used.

Statistics/facts characterizing the disorder

Fact #1: Genes COL1A1 and COL1A2 are responsible for 90% of all cases

Fact#2: Genes CRTAP and LEPRE1 are responsible for rare and fatal conditions.

Fact #3: A child of an affected parent has a 50% chance of inheriting the disease

Fact#4: New mutations occur sporadically and are usually first in the family

Statistic #1: an estimated 6 to 7 per 100,000 people worldwide are affected by OI

Statistic #2: most common forms (Type I and IV) affect 4 to 5 per 100,000 people

Statistic #3: 25-30% of cases occur in result of a new mutation

Statistic #4: Type I affects 1 out of 30,000 live births

Statistic #5: Type II affects 1 out of 60,000 live births

Statistic #6: Type III affects 1 out of every 70,000 live births

Did You Know?

  • Type VII is a rare recessive form that appears only in people living in in Quebec, Canada
  • A mummy from 1000 B.C on display at the British Museum in London, gives us evidence that Osteogenesis Imperfecta has been affecting people since ancient times
  • There are higher incidences of OI in 2 major tribal groups in Zimbabwe


What chromosomes are involved?

COL1A1 gene-Chromosome 17 the long arm position 21.33

COL1A2 gene- Chromosome 7 the long arm position 22.1

CRTAP gene- Chromosome 3 the short arm position 22.3

LEPRE1 gene- Chromosome 1 the short arm position 34.1

What is the inheritance pattern?

If one parent has it there is high chance that the offspring will get it

Most commonly autosomal dominance, but there are some cases of autosomal recessive:

  • COL1A1= Autosomal Dominant Pattern
  • COL1A2= Autosomal Dominant Pattern
  • CRTAP= Autosomal Recessive Pattern
  • LEPRE1= Autosomal Recessive Pattern

How is the DNA/gene affected? Is there a mutation? if so, what type of mutation?

COL1A1- Over 400 mutations
  • Type I- Substitution= reduction of Type I collagen
  • Types II, III, IV- Substitution= chains not organized properly

COL1A2- About 300 mutations

  • Type I- A few mutations
  • Type II, III, IV- prevent normal production of Type I collagen

CRTAP- "cartilage associated protein" gene

  • Type VII-5 mutations, prevents the gene from functioning
LEPRE1-"leucine proline-enriched proteoglycan (leprecan) 1" gene
  • Type VIII- at least 4 mutations= production of abnormal collagen


How does the mutation affect the structure and function of the protein or enzyme to be made?

COL1A1- protein segments off the end of the chromosome are removed by enzymes outside of the cell, causes the creation of a rope-like molecule containing 3 chains: 2 pro-a1(I) chains and 1 pro-a1(i) chain, collagen is present but the number of pro-a1(I) is reduced, cells only make some type 1 collagen, which leads to characteristic features of type I

COL1A2- prevents normal production of type 1 collagen which causes severe symptoms

How does that affect the individual?

To connect the genes to proteins to the symptoms we must start at the genetic changes. Along many places in the chains, genetic changes may occur with the replacement of one amino acid with another protein building block. For example, substitutions at the end of a protein chain will cause the chain to be not properly organized. Therefore, an abnormal collagen causes the most severe forms of OI.

Works Consulted

Picture 1: http://vitanetonline.com/forums/1/Thread/1640

Picture 2: http://dnadiseases.weebly.com/osteogenesis-imperfecta.html

Picture 3: http://dnadiseases.weebly.com/osteogenesis-imperfecta.html

Picture 4: http://dnadiseases.weebly.com/osteogenesis-imperfecta.html

Picture 5: https://ghr.nlm.nih.gov/gene/COL1A1

Picture 6: https://ghr.nlm.nih.gov/gene/COL1A2

Picture 7: https://ghr.nlm.nih.gov/gene/CRTAP


"Facts about Osteogenesis Imperfecta." Osteogenesis Imperfecta Foundation. Osteogenesis Imperfecta Foundation, Aug. 2015. Web. 2 Apr. 2016. <http://www.oif.org/site/PageServer?pagename=AOI_Facts>.

"Osteogenesis Imperfecta." Genetics Home Reference. U.S. National Lib. of Medicine, 21 Mar. 2016. Web. 29 Mar. 2016. <https://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta>.

"Osteogenesis Imperfecta (OI)." Encyclopedia of Human Genetics and Disease. Evelyn B. Kelly. Vol. 2. Santa Barbara, CA: Greenwood, 2013. 613-618. Gale Virtual Reference Library. Web. 24 Mar. 2016.

"Osteogenesis imperfecta (OI)." Britannica School.Encyclopædia Britannica, Inc., 2016. Web. 24 Mar. 2016. <http://school.eb.com/levels/high/article/57592>.

"20 Notable Osteogenesis Imperfecta Statistics." Health Research Funding. HealthResearchFunding.org, 6 Dec. 2014. Web. 2 Apr. 2016. <http://healthresearchfunding.org/20-notable-osteogenesis-imperfecta-statistics/>.